Brain and body temperature homeostasis during sodium pentobarbital anesthesia with and without body warming in rats
Introduction
General anesthesia is a procedure commonly used in neurobiological research, including studies of neuronal activity and responsiveness, alterations of blood flow, and body temperature regulation. While it is known that most drugs used for general anesthesia inhibit brain metabolism, decrease cerebral blood flow, and induce body hypothermia [4], [6], [17], [22], [26], several aspects of brain–body temperature homeostasis during general anesthesia remain unclear. Although data obtained in acute experiments suggest that anesthesia also results in robust brain hypothermia [5], [18], [29], [32], the extent and time-course of brain temperature changes and their relation to body core temperature during the development of and recovery from anesthesia have not been thoroughly studied. By studying the relative changes in brain and body core temperature during an anesthetic state, it becomes possible to clarify whether brain hypothermia reflects primarily inhibition of brain metabolism and thus has an intra-brain origin, or occurs due to body cooling related to general inhibition of metabolism. Since anesthesia results in peripheral vasodilatation and enhanced heat dissipation to the external environment [26], anesthesia should affect skin temperature, which reflects both the state of vessel tone and arterial blood temperature [1]. This parameter is studied little in relation to brain and body core temperatures during the development of and recovery from anesthesia. Finally, although body warming is commonly used during experimental anesthesia in animals to counteract heat loss and increase body core temperature, it remains unknown how this procedure affects brain temperature.
To clarify these issues, temperatures were simultaneously recorded from the brain, body core, and subcutaneously in awake, unrestrained rats during sodium pentobarbital-induced anesthesia, a procedure commonly used in animal research and a prototype of general anesthesia used in humans. Using a within-animal design, measurements were performed in the same animals during anesthesia in two conditions: at normal environmental temperatures (23 °C) and when body temperature was maintained at normal (37.5 °C) levels by external body warming. By tracking temperature responses in different brain and body sites with a short collection interval one should be able to map the dynamics of heat generation, flow, and loss within the organism.
For brain recording sites, we chose two structures, which differed in their functions, dorso-ventral location, and basal temperatures. The ventrally located medial preoptic area of the hypothalamus (MPAH) is a structure considered to be the primary thermointegrative center [25] and has a high basal temperature. The more dorsally located hippocampus (Hippo) was chosen as a control structure, which has significantly lower basal temperatures [9]. Because of the requirements of long-term monitoring in freely moving rats, core body and skin temperatures were assessed by miniature thermocouple sensors that were chronically implanted in, respectively, the retroperitoneal space and subcutaneously in the forehead area.
Section snippets
Subjects and surgery
Six male Long–Evans rats (Taconic, Rockville, MD), 3–4 months in age and 440±30 g in weight, housed individually (12-h light cycle beginning at 7:00) with free access to food and water, were used. Protocols were performed in compliance with the Guide for the Care and Use of Laboratory Animals (NIH Publication 865–23) and were approved by the Animal Care and Use Committee, NIDA-IRP. Under Equithesin anesthesia (3.3 ml/kg), each rat was implanted with four thermocouple probes in two brain sites
Time-course of temperature changes during anesthesia without and with body warming
Fig. 1 shows the temperature in each recording location following pentobarbital injection both without (left; control) and with (right) body heating. Significant differences in basal temperature (i.e., temperature immediately prior to injection) existed between the sites (MPAH 37.36±0.28 °C≈body core 37.40±0.32 °C>Hippo 36.65±0.23 °C>skin 35.30±0.27 °C; p<0.05, Student's t-test). In control conditions (no body warming), pentobarbital induced a strong (3.2–4.3 °C) and long-term (∼260 min)
Discussion
This study demonstrates that pentobarbital anesthesia is accompanied by robust brain hypothermia (from 36.5–37.5 °C to 32–33 °C, or –4.0–4.5 °C below baseline) in rats. While this finding confirms results obtained in monkeys [6], cats [5], and dogs [29], high-speed monitoring revealed that temperature decreases in brain sites precede and are larger than those in body core and skin (Fig. 2). Therefore, it appears that inhibition of brain metabolism, a known action of sedative-hypnotic,
Acknowledgement
We greatly appreciate Dr. Barry Hoffer for valuable comments on the subject of the present paper.
References (32)
- et al.
State-dependent action of cocaine on brain temperature and movement activity: implications for movement sensitization
Pharmacol Biochem Behav
(2004) - et al.
Fluctuations in brain temperatures during sexual behavior in male rats: an approach for evaluating neural activity underlying motivated behavior
Neuroscience
(2003) - et al.
Localized thermal changes evoked in the brain by visual and auditory stimulation
Exp Neurol
(1967) Intracerebral temperature in neurosurgical patients: intracerebral temperature gradients and relationships to consciousness level
Surg Neurol
(1995)- et al.
Synchronous changes in ear and tail blood flow following salient and noxious stimuli in rabbits
Brain Res
(1999) Nonlinear temperature modulation of sodium channel kinetics in GH3 cells
Biochim Biophys Acta
(2001)- et al.
Anesthetic technique influences brain temperature during cardiopulmonary bypass in dogs
Ann Thorac Surg
(1998) - et al.
On the role of anesthesia on the body/brain temperature differential in rats
J Therm Biol
(2004) - et al.
Variability of skin temperature in the waking monkey
Am J Physiol
(1976) - et al.
Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury
J Cereb Blood Flow Metab
(1987)